When to Get Tested?

Sample Required?

Test Preparation Needed?

Foods such as coffee (including decaf), tea, chocolate, vanilla, bananas, oranges and other citrus fruits should be avoided for several days prior to the test and during collection. There are also many medications that can potentially affect test results. Talk to your doctor about any prescriptions and over-the-counter drugs and supplements that you are taking. Wherever possible, those that are known to interfere should be discontinued prior to and during sample collection. Emotional and physical stresses and vigorous exercise should be minimized prior to and during test collection as they can increase catecholamines secretion.

The Test Sample

What is being tested?

This test measures the amounts of metanephrine and normetanephrine that are excreted in the urine over a 24-hour period. Metanephrine and normetanephrine are the inactive metabolites of the catecholamines epinephrine (adrenaline) and norepinephrine. Catecholamines are a group of similar hormones produced in the medulla (central portion) of the adrenal glands. The adrenal gland is a small, triangular organ located on top of each kidney.

The primary catecholamines are dopamine, epinephrine (adrenaline), and norepinephrine. These hormones are released into the bloodstream in response to physical or emotional stress. They help transmit nerve impulses in the brain, increase glucose and fatty acid release for energy, dilate small air passages in the lungs called bronchioles, and dilate the pupils. Norepinephrine also constricts blood vessels, which increases blood pressure, and epinephrine increases heart rate and metabolism. After completing their actions, the catecholamines are metabolized to form inactive compounds. Dopamine becomes homovanillic acid (HVA), norepinephrine breaks down into normetanephrine and vanillylmandelic acid (VMA), and epinephrine becomes metanephrine and VMA. Both the hormones and their metabolites are excreted in the urine.

Urine metanephrines testing measures the amount of both metanephrine and normetanephrine. These metabolites are usually present in the urine in small fluctuating amounts that increase appreciably during and shortly after the body is exposed to a stressor. Rare pheochromocytomas and other neuroendocrine tumors, however, can produce large amounts of catecholamines, resulting in greatly increased concentrations of the hormones and their metabolites in both the blood and urine. The catecholamines that a pheochromocytoma produces can cause persistent hypertension (high blood pressure) and episodes of severe hypertension. Other symptoms of catecholamine release include headaches, palpitations, sweating, nausea, anxiety, and tingling in the extremities.

About 90% of pheochromocytomas are located in the adrenal glands. While a few are cancerous, most are benign – they do not spread beyond their original location – although most do continue to grow. Left untreated, the symptoms may worsen as the tumor grows and, over a period of time, the hypertension from a pheochromocytoma may cause kidney damage, heart disease, and raise the risk of a stroke or heart attack.

The metanephrines test can be used to help detect the presence of pheochromocytomas. Although, according to the National Cancer Institute, only about 800 cases a year are diagnosed in the U.S., it is important to diagnose and treat these rare tumors because they cause a potentially curable form of hypertension. In most cases, the tumors can be surgically removed and/or treated to significantly reduce the amount of catecholamines being produced and to reduce or eliminate associated symptoms and complications.

How is the sample collected for testing?

For the 24-hour urine collection, all urine should be saved for a 24-hour period. It is important that the sample be refrigerated during this time period.

Another article, Follow That Sample, provides a glimpse at the collection and processing of a blood sample and throat culture.

Is any test preparation needed to ensure the quality of the sample?

Foods such as coffee (including decaf), tea, chocolate, vanilla, bananas, oranges and other citrus fruits should be avoided for several days prior to the test and during collection. There are also many medications that can potentially affect test results. People being tested should talk to their doctor about prescriptions and over-the-counter drugs and supplements that they are taking. Wherever possible, substances that are known to interfere should be discontinued prior to and during sample collection. However, it is important to consult with the doctor before stopping any medications. Emotional and physical stresses and vigorous exercise should be minimized prior to and during sample collection as they can increase catecholamines secretion.

The Test

How is it used?

Urine metanephrines testing is primarily used to help detect and rule out pheochromocytomas in symptomatic people. It may also be ordered to help monitor the effectiveness of treatment when a pheochromocytoma is removed to monitor for recurrence. Urine metanephrines testing may be ordered by itself or along with a plasma metanephrines test. Plasma and urine catecholamines testing may also be ordered, either along with urine metanephrines or as follow-up tests. Since catecholamines secretion tends to fluctuate over time, a 24-hour urine test for metanephrines or catecholamines may detect excess production that is missed with the blood test. It is up to the doctor to decide which test or test combinations will give him the most information. In many cases, urine and plasma metanephrines may be preferred as they are usually present in greater quantities than catecholamines in the urine and can persist in the blood even when catecholamine levels have returned to normal.

Since these tests are affected by drugs, foods, and stresses, false positive tests may occur. For this reason, metanephrines testing is not recommended as a screen for the general public. Doctors will frequently investigate a positive result by evaluating a person's stress, diet, and medications, work to alter or minimize these influences, and then repeat the test to confirm the original findings.

Occasionally, metanephrines testing may be ordered on an asymptomatic person if an adrenal or neuroendocrine tumor is detected during a scan that is done for another purpose or if the person has a strong personal or family history of pheochromocytomas (as they may recur and there is a genetic link in some cases).

When is it ordered?

Urine metanephrines are ordered when a doctor either suspects that someone has a pheochromocytoma or wants to rule out the possibility. He may order it when a person has persistent or recurring hypertension along with symptoms such as headaches, sweating, flushing, and rapid heart rate. It may also be ordered when a person has hypertension that is not responding to treatment. Since the hormone production from a pheochromocytoma is not regulated by the body, those who have hypertension due to a pheochromocytoma are frequently resistant to conventional therapies.

Occasionally, the test may be ordered when an adrenal tumor is detected incidentally or when someone has a family history of pheochromocytomas. It also may be used as a monitoring tool when a person has been treated for a previous pheochromocytoma.

What does the test result mean?

Because the urine metanephrines test is sensitive to many outside influences and pheochromocytomas are rare, a doctor may see more false positives with this test than true positives. If a symptomatic person has large amounts of metanephrine and/or normetanephrine in his urine, further investigation is indicated. If there are no interfering substances or stresses identified, then there is a good possibility that he may have a pheochromocytoma. The doctor may order plasma metanephrines and/or urine or plasma catecholamines testing to help confirm the initial findings. If these are also elevated, then imaging tests such as an MRI may be ordered to help locate the tumor(s).

Serious illnesses and stresses can cause moderate to large temporary increases in metanephrines levels. Doctors must evaluate the person as a whole – his physical condition, emotional state, medications, and diet. When interfering substances and/or conditions are found and resolved, the doctor will frequently re-test the person to determine whether the metanephrines are still elevated. If they are, then he may order imaging scans; if they are not, then it is unlikely that the person has a pheochromocytoma.

If levels are elevated in someone who has had a previous pheochromocytoma, it is likely that either treatment was not fully effective or that the tumor is recurring.

The negative predictive value of the test is relatively good. This means that if metanephrine and normetanephrine concentrations are normal, then it is unlikely that a person has a pheochromocytoma.

Is there anything else I should know?

While metanephrines testing can help detect and diagnose pheochromocytomas, it cannot tell the doctor how big the tumor is, where it is, how many tumors are present, or whether or not the tumor(s) are benign – although most are. Even small tumors can produce large amounts of catecholamines.

It is very important to talk to the doctor before discontinuing any prescribed medications. He will work with the person being tested to identify interfering substances and drug treatments to determine which of them can be safely interrupted and which must be continued for a person's well-being. Some of the substances that can interfere with metanephrine testing include: acetaminophen, aminophylline, amphetamines, appetite suppressants, coffee, tea, and other forms of caffeine, chloral hydrate, clonidine, dexamethasone, diuretics, epinephrine, ethanol (alcohol), insulin, imipramine, lithium, methyldopa (Aldomet), MAO (monoamine oxidase) inhibitors, nicotine, nitroglycerine, nose drops, propafenone (Rythmol), reserpine, salicylates, theophylline, tetracycline, tricyclic antidepressants, and vasodilators. The effects of these drugs on metanephrines testing will be different from person to person and are often not predictable.

5. Is it really necessary to collect urine for 24 hours?

Yes, for accurate test results it is essential that all of the urine be collected. Because the catecholamines are released at varying times, one sample might not be sufficient to detect the average concentration of metanephrines.

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NOTE: This article is based on research that utilizes the sources cited here as well as the collective experience of the Lab Tests Online Editorial Review Board. This article is periodically reviewed by the Editorial Board and may be updated as a result of the review. Any new sources cited will be added to the list and distinguished from the original sources used.

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This article was last reviewed on February 24, 2012. | This article was last modified on February 26, 2013.

The review date indicates when the article was last reviewed from beginning to end to ensure that it reflects the most current science. A review may not require any modifications to the article, so the two dates may not always agree.

The modified date indicates that one or more changes were made to the article. Such changes may or may not result from a full review of the article, so the two dates may not always agree.